The candidate of this K23 Mentored Patient-Oriented Research Career Development Award, Stanislav R. Vorel, MD PhD, requests support for a program of research and training aimed at developing expertise in conducting translational research in the area of treatment development for substance use disorders and achieving a long-term goal of becoming an independent investigator. Dr. Vorel proposes a career development plan that is built on his background in behavioral neuroscience of substance abuse and clinical psychiatry and will take advantage of the resources of Columbia University's extensive network of basic and clinical programs in substance abuse pharmacotherapy trials. A comprehensive plan that includes coursework, research, and mentoring provides training in 1) human laboratory methodologies;and 2) (the design, methodology and logistics of clinical trials. In addition, a research plan focuses on developing a new approach to the treatment of nicotine dependence by combining behavioral therapy (cue-extinction procedure) and medications (nicotine substitution and a glutamatergic medication d-cycloserine: DCS). The research plan includes a laboratory "proof-of-concept" study that will inform a subsequent small-scale efficacy treatment trial. Nicotine craving triggered by smoking cues contributes to relapse in abstinent individuals maintained on nicotine replacement. Repeated exposure to smoking cues may result in a decrease or extinction of nicotine craving in the laboratory and lower relapse rates after smoking cessation. The study's main hypothesis is that DCS facilitates cue exposure therapy and may prevent relapse to smoking. The aim of study 1 is to develop an extinction procedure to smoking cues and to assess if this procedure results in subsequent improved abstinence. The aim of study 2 is to assess whether DCSfaciiitation of cue-exposure therapy improves abstinence among smokers on the nicotine patch. The overarching goal of this proposal is to advance Dr. Vorel towards an independent research career pursuing innovative treatments for smoking cessation. The mentors specialize in laboratory and clinical studies in substance abuse. The site has an established program and track record in training addiction researchers. PUBLIC HEALTH RELEVANCE: Nicotine dependence contributes to significant morbidity and mortality in our society. Current treatments, including popular nicotine replacement therapies (NRT) face high relapse rates. Development of an effective treatment strategy to enhance the effectiveness of NRTs would have a direct and significant positive impact on public health.